Fans will now be expecting Team Fury to take on some tougher challenges in next fights, with the The Gypsy King due to be back out on the Carl Frampton undercard on August 18 in Belfast.
Former world champion Tyson fury (26-0, 19 KO's) won his first fight after his return, forcing the Sefer Sefer (23-2, 21 KOs) seem.
An early right hand over the top from Seferi drew a smile from Fury, who spent much of the opener playing to the crowd rather than throwing any punches.
Promoter Frank Warren plans on Fury fighting again at Windsor Park in Belfast on August 18, on the undercard of WBO interim featherweight champion Carl Frampton's next fight.
Following his victory, the British boxer described the return to the ring as "fantastic".
I learned two and a half years is a long time to be out.
"I could have knocked him out in the first round but what good would that have done me?"
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The difference in weight between the fury and the Sefer was nearly 30 kg, whereas the difference in height - 26 cm in such hands equal match could not be, but as it turned out, the Manchester Boxing was not at all.
"I hoped for a bigger opponent but we couldn't really get anyone, there was no one available".
Seferi, who was almost five stones lighter and seven inches smaller, did show some ambition early on but Fury's height and movement ensured there was never going to be an upset at Manchester Arena.
The Albanian Seferi was immediately put off and was pulled out of the fight before the start of the fifth round. He needs to get the ring rust off.
After the fight, Fury was just glad to be back in the ring.
Joshua and Deontay Wilder, the American who holds the World Boxing Council (WBC) belt, remain distant targets for Fury as they are in talks to face each other.
Former heavyweight champion Fury had not fought since dethroning Ukrainian Wladimir Klitschko in 2015 and suffered various drug, alcohol and mental health issues since then. He looked in reasonable shape on his comeback, although still has some weight to lose before his next outing.